Saratin (an inhibitor of platelet-collagen interaction) decreases platelet aggregation and homocysteine-mediated postcarotid endarterectomy intimal hyperplasia in a dose-dependent manner - 25/08/11

Doi : 10.1016/j.amjsurg.2004.08.061

Joseph A. Davis, M.D. ^a, Aliza T. Brown, Ph.D. ^a, Tarek Alshafie, M.D. ^a, Lionel A. Poirier, Ph.D. ^b, Carlos P. Cruz, M.D. ^a, Yunfang Wang, M.S. ^a, John F. Eidt, M.D. ^a, Mohammed M. Moursi, M.D. ^a,⁎
^a University of Arkansas for Medical Sciences, Central Arkansas Veterans HealthCare System, Vascular Service, 112/PV, Little Rock, AR 72205, USA
^b Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AR, USA

^*Corresponding author. Tel.: +1-501-257-6863; fax: +1-501-257-6863.

Abstract

Background

This study investigated Saratin’s (Merck KGaA, Darmstadt, Germany) prevention of platelet adhesion and intimal hyperplasia at different doses and in the hyperhomocystinemia rat carotid endarterectomy (CEA) model.

Methods

Rats were divided into two groups: (1) platelet adhesion or (2) luminal stenosis because of intimal hyperplasia. At CEA, rats received 0, 0.5, 5.0, 10.0, or 20.0 μg Saratin on the artery. Post-CEA platelet aggregation was evaluated by standard error of the mean. Intimal hyperplasia group received either (1) control or (2) 4.5 g/kg DL-homocystine diets for two weeks followed by CEA and treated with diluent or 5.0 μg Saratin. Endpoints included platelet adhesion, intimal hyperplasia, plasma homocysteine (HCys), and its metabolic enzymes cystathionine β-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR).

Results

Platelet adhesion: post-CEA, platelet adhesion was reduced by 63%, 67%, and 67% in Saratin doses ≥5.0 μg. Intimal hyperplasia: 5.0 μg Saratin in the HCys group decreased intimal hyperplasia by 45% compared with the non-Saratin-treated HCys group. Plasma HCys levels were not altered with Saratin treatment in the HCys groups nor were CBS or MTHFR.

Conclusions

Saratin significantly inhibited platelet adhesion at ≥5.0 μg, and Saratin at 5.0 μg attenuated luminal stenosis in a hyperhomocysteinemic rat CEA model.

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Keywords : Carotid endarterectomy, Saratin, Intimal hyperplasia, Homocysteine, Platelet